TS-000972 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. When an NK cell is deficient or dysfunctional, the efficiency of the NK cells is severely limited. VISTA is a protein sequence that activates T cells and acts as a moderator for the immune system. It has low-to-moderate expression but has been the target of study by a team of researchers at Nationwide Children’s Hospital led by Dr. Dean Lee. By removing VISTA in expanded NK cells, the inhibitory signal will be eliminated and thus resulting in an enhanced ability of NK cells to target cancers and overcome the immune-suppressive signals for improved cancer immunotherapy.

TS-000969 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. Chimeric Antigen Receptor T cells (CAR T) are comprised of an extracellular antigen recognition domain, intracellular T cell activation and co-stimulatory domains. These cells allow for potent and specific targeting of cancer cells, bypassing the need for antigen presentation and T cell receptor recognition. Generating CAR T cells using the process of lentiviral transduction has limitations stemming from the random integration of transgenesis, where oncogene activation, gene silencing, or negative effects on the CAR T antitumor efficacy are possible.

TS-000913 — Peptides can be used to stimulate antigen-specific T cells, allowing activated T cells to be isolated from immune individuals to be used in vaccination or treatment in others. The novel disease Coronavirus, also denoted as 2019-nCoV, was recognized by the World Health Organization as an unknown etiology in December of 2019. Severe Acute Respiratory Syndrome (SARS) is a disease that presents flu-like symptoms that is caused by coronavirus (SARS-CoV). A current process widely applicable to many pathogens uses the Miltenyi Prodigy device. In a study led by Dr. Dean Lee, his team found that this process can be adapted to SARS-CoV-2 using a specialty mix of peptides to isolate T cell immunity.

TS-000906 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. Additionally, CD38 presenting cells have been used as a marker for cancer stem cells, specifically those that often avoid recognition when common surface antigen processes are used. CARK1 is a phosphorylate that impacts cell growth and development. A team led by Dr. Dean Lee has developed CD38k0 NK cells that they combine with CARK1 to create a series of monoclonal antibodies that targets cancer cells. Along with better cell targeting, this combination improves the efficacy of treatment in comparison to the CAR, NK, or CD38 antibodies as independent components.

TS-000857 — CD33 is a receptor that spans multiple membranes and is expressed on myeloid lineage cells and sometimes lymphoid cells. A team of researchers led by Dr. Dean Lee have found a new way to modify existing CD33 processes to provide Natural Killer (NK) cells the additional ability to recognize cell targets expressing CD33. Acute Myeloid Leukemia (AML) expresses multiple antigens, where CD33 is the most common. This new process, labeled as CD33-CAR, shows a significant advantage in targeting AML that presents with CD33, especially in cases that resist unmodified NK cells.

TS-000841 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. In a group study it was found that by using TGFb-imprinting, NK cells are driven to a pro-inflammatory phenotype with hypersecretion of IFN-γ, TNF-α, and GM- CSF. These cells, now TGFbi, had decreased degrees of CD38 at both the RNA and the protein level. Studies performed by Drs. Dean Lee and Marcelo Pereira found that CD38 NK cells can be utilized to target CD38+ multiple myeloma patients and improve their progression-free survival by avoiding death of healthy surrounding cells, as well as enhancement of NK cell function.

TS-000834 — Cancer and their tumors create and thrive in a microenvironment that is highly immune suppressant. By targeting specific genes and genetically modifying natural killer (NK) cells, the clinical outcomes of cancer immunotherapy have the advanced ability to overcome these diseases. NK cells in solid tumors have been reported to exhibit an inactive and dysfunctional state, and expanded NK cells under hypoxic conditions showed a decrease in cytotoxic ability. Drs. Dean Lee and Marcelo Pereira found that by using the developed approach that focuses on Cas9/RNP, the HIF1a in NK cells can permanently overcome the effects of hypoxia without the noted disadvantages of small-molecule inhibitors.

TS-000446 — Airway epithelial cells (AECs) in the lungs play a crucial role in maintaining a conduit for air and defend against pathogens. Various acute and chronic pulmonary diseases damage AECs resulting in their altered structure and function. However, the AEC renewal is a slow process. Researchers at Nationwide Children’s Hospital have generated Airway Epithelial Stem cells using gene editing technology that will provide unlimited cell source for AECs. Notably, these cells evade immune rejection in recipients. This preclinical invention may provide “off-the-shelf” product paving the way to regenerative respiratory therapeutics.